Insertional Mutation of the <i>Drosophila</i> Nuclear Lamin Dm0 Gene Results in Defective Nuclear Envelopes, Clustering of Nuclear Pore Complexes, and Accumulation of Annulate Lamellae

Lenz‐Böhme, Bettina; Wismar, Jasmine; Fuchs, Silke; Reifegerste, Rita; Buchner, Erich; Betz, Heinrich; Schmitt, Bertram

doi:10.1083/jcb.137.5.1001

Cited by 217 publications

(175 citation statements)

References 85 publications

(121 reference statements)

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“…The function of AL is not well understood. Thus far, the only other genetic alteration that is known to promote AL formation is the disruption of the Drosophila nuclear lamin Dm 0 gene (21). Characteristically, lamin Dm 0 -deficient cells form large numbers of cytoplasmic AL, but do not exhibit major changes in the NPC density of their NEs.…”

Section: Discussionmentioning

confidence: 99%

Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function

Kasper

Mantcheva

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

131

122

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The NUP98 gene encodes precursor proteins that generate two nucleoplasmically oriented nucleoporins, NUP98 and NUP96. By using gene targeting, we have selectively disrupted the murine NUP98 protein, leaving intact the expression and localization of NUP96. We show that NUP98 is essential for mouse gastrulation, a developmental stage that is associated with rapid cell proliferation, but dispensable for basal cell growth. NUP98؊͞؊ cells had an intact nuclear envelope with a normal number of embedded nuclear pore complexes. Typically, NUP98-deficient cells contained on average approximately 5-fold more cytoplasmic annulate lamellae than control cells. We found that a set of cytoplasmically oriented nucleoporins, including NUP358, NUP214, NUP88, and p62, assembled inefficiently into nuclear pores of NUP98؊͞؊ cells. Instead, these nucleoporins were prominently associated with the annulate lamellae. By contrast, a group of nucleoplasmically oriented nucleoporins, including NUP153, NUP50, NUP96, and NUP93, had no affinity for annulate lamellae and assembled normally into nuclear pores. Mutant pores were significantly impaired in transport receptor-mediated docking of proteins with a nuclear localization signal or M9 import signal and showed weak nuclear import of such substrates. In contrast, the ability of mutant pores to import ribosomal protein L23a and spliceosome protein U1A appeared intact. These observations show that NUP98 disruption selectively impairs discrete protein import pathways and support the idea that transport of distinct import complexes through the nuclear pore complex is mediated by specific subsets of nucleoporins.T ransport between the nucleus and the cytoplasm occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope (NE). NPCs have an 8-fold rotational symmetry in the plane parallel to the NE (reviewed in ref. 1). Each NPC contains a membrane-embedded central framework that embraces a central pore. The central framework consists of a ring-like spoke complex that is sandwiched between a cytoplasmic and a nuclear ring. Each cytoplasmic ring supports eight fibrils that extend into the cytoplasm, whereas each nuclear ring carries eight filaments that join distally to form a basket-like assembly (1, 2). The vertebrate NPC has an estimated molecular mass of Ϸ125 MDa and is composed of Ϸ80-100 different proteins called nucleoporins, of which 16-20 have been cloned (3). In contrast, the Saccharomyces cerevisiae NPC is only Ϸ66 MDa (4) and is composed of Ϸ35-50 nucleoporins, of which more than 30 have now been identified (5).Nucleocytoplasmic transport is mediated by soluble transport factors that belong to the karyopherin family of transport receptors, whose members can be subdivided into importins and exportins. Typically, a given transport receptor binds to an import or export signal-containing cargo in one compartment, guides it to and accompanies it through an NPC, releases it in the opposite compartment, and then shuttles back to the first compartment to repeat the cycle (see r...

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Section: Discussionmentioning

confidence: 99%

Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function

Kasper

Mantcheva

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

131

122

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“…Reduction in levels of lamin Dm 0 activity in Drosophila and elimination of lamin A gene in mouse have both shown to yield abnormalities in the pattern of NPCs (Lenz-Bohme et al, 1997;Harel et al, 1998;Sullivan et al, 1999). We therefore compared the spatial organization of the NPCs in lmn-1 (RNAi) embryos and normal C. elegans embryos by staining them with monoclonal antibody MAb414, which recognizes the FG repeats present in many nucleoporins (Davis and Blobel, 1987).…”

Section: An Intact Nuclear Lamina Is Required For the Correct Spacingmentioning

confidence: 99%

“…These results suggest that the association of the nuclear lamina with the NPCs is required for their correct spacing. The role of the nuclear lamina in spacing NPCs is probably conserved in evolution since similar phenotypes are seen in lines with reduced Drosophila lamin Dm 0 and in mice lacking the lamin A gene (Lenz-Bohme et al, 1997;Harel et al, 1998;Sullivan et al, 1999). …”

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confidence: 99%

“…Flies homozygous for mutations in the lamin Dm 0 gene have aberrant nuclear structure and die after 9 to 14 h of development, as the maternal pool of lamin Dm 0 is diluted (Harel et al, 1998). Hypomorphic mutation in the lamin Dm 0 gene (Ͻ20% of lamin expression) causes reduced viability, defective nuclear envelopes, and accumulation of annulate lamellae (Lenz-Bohme et al, 1997).A search of the nearly complete genome of C. elegans reveals a single lamin gene, termed lmn-1. The lmn-1 gene is located on chromosome I, is 2.7-kb long, and is composed of 6 exons and 5 short introns (Riemer et al, 1993).…”

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confidence: 99%

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Essential Roles forCaenorhabditis elegansLamin Gene in Nuclear Organization, Cell Cycle Progression, and Spatial Organization of Nuclear Pore Complexes

Ben-Shahar

Riemer

et al. 2000

MBoC

379

360

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Caenorhabditis elegans has a single lamin gene, designated lmn-1 (previously termed CeLam-1). Antibodies raised against the lmn-1 product (Ce-lamin) detected a 64-kDa nuclear envelope protein. Ce-lamin was detected in the nuclear periphery of all cells except sperm and was found in the nuclear interior in embryonic cells and in a fraction of adult cells. Reductions in the amount of Ce-lamin protein produce embryonic lethality. Although the majority of affected embryos survive to produce several hundred nuclei, defects can be detected as early as the first nuclear divisions. Abnormalities include rapid changes in nuclear morphology during interphase, loss of chromosomes, unequal separation of chromosomes into daughter nuclei, abnormal condensation of chromatin, an increase in DNA content, and abnormal distribution of nuclear pore complexes (NPCs). Under conditions of incomplete RNA interference, a fraction of embryos escaped embryonic arrest and continue to develop through larval life. These animals exhibit additional phenotypes including sterility and defective segregation of chromosomes in germ cells. Our observations show that lmn-1 is an essential gene in C. elegans, and that the nuclear lamins are involved in chromatin organization, cell cycle progression, chromosome segregation, and correct spacing of NPCs. INTRODUCTIONThe nuclear lamina is a filamentous meshwork that is present between the inner nuclear membrane and the peripheral chromatin. The inner nuclear membrane and the nuclear lamina are involved in organizing nuclear structure and regulating nuclear events. These include the organization of the higher order structure of chromatin and regulation of nuclear assembly and disassembly. The nuclear lamina is a primary target for caspases in apoptosis (reviewed in Goldberg et al., 1999b). Lamins are the major proteins of the nuclear lamina. They are classified as type-V intermediate filaments and are composed of an ␣-helical rod domain flanked by a short amino (head) and a long carboxy (tail) domains. The rod domain of lamins is 52-nm long and contains four ␣-helices, each composed of heptad repeats. Coiled-coil interactions and head-to-tail associations between lamin monomers form 10-to 200-nm thick lamin filaments (reviewed in Stuurman et al., 1998) In vivo, lamin filaments are closely associated with the chromatin fibers (Belmont et al., 1993). In vitro, lamins can bind interphase chromatin (Hoger et al., 1991;Yuan et al., 1991;Taniura et al., 1995;Ulitzur et al., 1997;Goldberg et al., 1999a), mitotic chromosomes (Glass and Gerace, 1990;Glass et al., 1993), or specific DNA sequences (Shoeman and Traub, 1990;Luderus et al., 1992;Luderus et al., 1994;Baricheva et al., 1996;Zhao et al., 1996). The binding site of vertebrate lamins to chromatin is localized to specific sequences in the tail domain and can be displaced with the core histones H2A and H2B (Taniura et al., 1995;Goldberg et al., 1999a).The composition of the nuclear lamina varies in different cell types and is under developmental regulation ...

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“…In Drosophila, where no cytoplasmic IF genes have been found, there are two nuclear lamin genes, DM 0 and C. Genetic analyses have shown that DM 0 is essential for nuclear organization, and mutations in this gene result in the formation of abnormal nuclear envelopes, nuclear pore clustering, and the accumulation of annulate lamellae, the storage forms of nuclear envelopes. This produces severe defects, including slow developmental progression, sterility, and impaired locomotion (20).…”

Section: Ntermediate Filaments (If) Representmentioning

confidence: 99%

Worms reveal essential functions for intermediate filaments

Goldman

2001

Proc. Natl. Acad. Sci. U.S.A.

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Insertional Mutation of the Drosophila Nuclear Lamin Dm0 Gene Results in Defective Nuclear Envelopes, Clustering of Nuclear Pore Complexes, and Accumulation of Annulate Lamellae

Cited by 217 publications

References 85 publications

Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function

Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function

Essential Roles forCaenorhabditis elegansLamin Gene in Nuclear Organization, Cell Cycle Progression, and Spatial Organization of Nuclear Pore Complexes

Worms reveal essential functions for intermediate filaments

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